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The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma
BACKGROUND: Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma....
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695475/ https://www.ncbi.nlm.nih.gov/pubmed/19473536 http://dx.doi.org/10.1186/1471-2407-9-162 |
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author | Liu, Suhu Howell, Paul Ren, Suping Fodstad, Oystein Riker, Adam I |
author_facet | Liu, Suhu Howell, Paul Ren, Suping Fodstad, Oystein Riker, Adam I |
author_sort | Liu, Suhu |
collection | PubMed |
description | BACKGROUND: Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma. METHODS: The methylation status of 14-3-3σ CpG island in melanocytes and melanoma cells was analyzed by methylation-specific sequencing (MSS) and quantitative methylation-specific PCR (Q-MSP). 14-3-3σ mRNA and protein expression in cell lines was detected by real-time RT-PCR and western blot. Melanoma cells were also treated by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and/or histone deacetylase inhibitor, Trichostatin A (TSA), to evaluate their effects on 14-3-3σ gene expression. RESULTS: 14-3-3σ is hypermethylated in both human melanocytes and most melanoma cells in a lineage-specific manner, resulting in the silencing of 14-3-3σ gene expression and the active induction of 14-3-3σ mRNA and protein expression following treatment with DAC. We also observed a synergistic effect upon gene expression when DAC was combined with TSA. The promoter methylation status of 14-3-3σ was analyzed utilizing Q-MSP in 20 melanoma tissue samples and 10 cell lines derived from these samples, showing that the majority of melanoma samples maintain their hypermethylation status of the 14-3-3σ gene. CONCLUSION: 14-3-3σ is hypermethylated in human melanoma in a cell-linage specific manner. Spontaneous demethylation and re-expression of 14-3-3σ is a rare event in melanoma, indicating 14-3-3σ might have a tentative role in the pathogenesis of melanoma. |
format | Text |
id | pubmed-2695475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26954752009-06-12 The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma Liu, Suhu Howell, Paul Ren, Suping Fodstad, Oystein Riker, Adam I BMC Cancer Research Article BACKGROUND: Recent evidence demonstrates that 14-3-3σ acts as a tumor suppressor gene inactivated by methylation of its 5' CpG islands in epithelial tumor cells, while remaining un-methylated in normal human epithelia. The methylation analysis of 14-3-3σ has been largely overlooked in melanoma. METHODS: The methylation status of 14-3-3σ CpG island in melanocytes and melanoma cells was analyzed by methylation-specific sequencing (MSS) and quantitative methylation-specific PCR (Q-MSP). 14-3-3σ mRNA and protein expression in cell lines was detected by real-time RT-PCR and western blot. Melanoma cells were also treated by 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and/or histone deacetylase inhibitor, Trichostatin A (TSA), to evaluate their effects on 14-3-3σ gene expression. RESULTS: 14-3-3σ is hypermethylated in both human melanocytes and most melanoma cells in a lineage-specific manner, resulting in the silencing of 14-3-3σ gene expression and the active induction of 14-3-3σ mRNA and protein expression following treatment with DAC. We also observed a synergistic effect upon gene expression when DAC was combined with TSA. The promoter methylation status of 14-3-3σ was analyzed utilizing Q-MSP in 20 melanoma tissue samples and 10 cell lines derived from these samples, showing that the majority of melanoma samples maintain their hypermethylation status of the 14-3-3σ gene. CONCLUSION: 14-3-3σ is hypermethylated in human melanoma in a cell-linage specific manner. Spontaneous demethylation and re-expression of 14-3-3σ is a rare event in melanoma, indicating 14-3-3σ might have a tentative role in the pathogenesis of melanoma. BioMed Central 2009-05-27 /pmc/articles/PMC2695475/ /pubmed/19473536 http://dx.doi.org/10.1186/1471-2407-9-162 Text en Copyright ©2009 Liu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Liu, Suhu Howell, Paul Ren, Suping Fodstad, Oystein Riker, Adam I The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
title | The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
title_full | The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
title_fullStr | The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
title_full_unstemmed | The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
title_short | The 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
title_sort | 14-3-3σ gene promoter is methylated in both human melanocytes and melanoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695475/ https://www.ncbi.nlm.nih.gov/pubmed/19473536 http://dx.doi.org/10.1186/1471-2407-9-162 |
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